Reassurance against future risk of precancer and cancer conferred by a negative human papillomavirus test

Abstract

Primary human papillomavirus (HPV) testing (without concurrent Pap tests) every 3 years is under consideration in the United States as an alternative to the two recommended cervical cancer screening strategies: primary Pap testing every 3 years, or concurrent Pap and HPV testing ("cotesting") every 5 years. Using logistic regression and Weibull survival models, we estimated and compared risks of cancer and cervical intraepithelial neoplasia grade 3 or worse (CIN3+) for the three strategies among 1011092 women aged 30 to 64 years testing HPV-negative and/or Pap-negative in routine screening at Kaiser Permanente Northern California since 2003. All statistical tests were two sided. Three-year risks following an HPV-negative result were lower than 3-year risks following a Pap-negative result (CIN3+ = 0.069% vs 0.19%, P < .0001; Cancer = 0.011% vs 0.020%, P < .0001) and 5-year risks following an HPV-negative/Pap-negative cotest (CIN3+ = 0.069% vs 0.11%, P < .0001; Cancer = 0.011% vs 0.014%, P = .21). These findings suggest that primary HPV testing merits consideration as another alternative for cervical screening.

Figure 1.

Cumulative risks of cervical intraepithelial neoplasia grade 2 or more severe (left panel), grade 3 or more severe (center panel) and cancer (right panel) among women aged 30 to 64 years at Kaiser Permanente Northern California by enrollment Pap and human papillomavirus (HPV) test result, 2003 to 2012. Women are HPV-negative if they tested negative by Hybrid Capture 2 (hc2; Qiagen, Germantown, MD), an assay that tests for 13 high-risk HPV genotypes (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68). Among 1011092 (97.5%) women testing HPV-negative and/or Pap-negative, 980268 tested Pap-negative alone (regardless of HPV result), 923706 women tested HPV-negative alone (regardless of Pap result) and 892882 women tested cotest-negative. Briefly, the cumulative risks were obtained by adding the risk at enrollment test (using logistic regression) to the risk after enrollment (using Weibull survival modeling). Note that the y axes have different scales for different panels. Risk bands are 95% confidence intervals. All statistical tests were two sided. CIN2 = cervical intraepithelial neoplasia grade 2; CIN3 = cervical intraepithelial neoplasia grade 3; HPV = human papillomavirus.